Ificant relationship to synaptic numbers in either lamina (Scheff et al., 1990; Scheff and Price, 1993, 2001). Recent data suggests that the amyloid toxic moiety is the oligomeric component of A (Lacor et al. 2007), which damages synapses (Lacor et al., 2007) and results in cognitive impairment (Lesne et al., 2006; Tu et al., 2014). Therefore, further clinical pathological studies are required to determine the relationship between hippocampal plasticity and the oligomeric forms of A as well as other components of proteolytically processed APP, including the C-terminal fragment of APP and other metabolites.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptHippocampal Plasticity and Brain ReserveKatzman et al., 1988, first introduced the concept of the brain reserve to explain hippocampal structural and biochemical plasticity in the course of AD. Post-mortem examinations in 137 elderly persons revealed a discrepancy between the degree of AD neuropathology and the clinical manifestations at the time of death. Some subjects whose brains had extensive AD pathology had no or very little clinical manifestations of the get Ornipressin disease (Katzman et al., 1988). Similar results have since been reported by a number of other investigators (e.g., Mufson et al., 1999; Price et al. 2009, Markesbery et al., 2009; Mufson et al., 2014; Schneider et al., 2009). The seminal paper by Katzman et al. (1988) also reported that these persons had higher brain weights and greater number of neurons as compared to age-matched controls, leading the authors to propose two possible explanations for this phenomenon: these people may have had incipient AD but by some as-yet unknown factor avoided the loss of large numbers of neurons, or alternatively, began with Lixisenatide site larger brains and more neurons. This led to the concept of a greater brain “reserve”, which might allow for synaptic remodeling as a compensatory mechanism to the early pathobiology of the disease and in turn be able to maintain cognitive abilities in the prodromal stages of the dementia (Mufson et al., 1999; Katzman et al., 1988; Snowdon et al., 1996; Mortimer et al., 1988; DeKosky et al., 2002). It has been suggested that neuroplastic responses are lost as an individual’s dementia progresses (Mesulam, 1999) leading to the consistent observation of a reduction in neuronal viability (Gilmor et al., 1999) and activity in the hippocampus in late-Neuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagestage AD (DeKosky et al., 2002; Iknonomovic et al., 2003; Davis et al., 1999). An additional phase of plasticity, not evoked until later in the disease, is the development of a neuroplastic response by the inhibitory neuropeptide, galanin (GAL), a G-protein coupled receptor that mediates neurotransmission in the basal forebrain, entorhinal cortex, hippocampus and amygdala (Habert-Ortoli et al., 1994; Smith et al., 1998; Kolakowski et al., 1998; Dutar et al., 1989, Fisone et al., 1987; Coumis et al., 2002; Hartonian et al., 2002; Jhamandas et al., 2002; Mazarati et al., 2000; McDonald et al., 1998; Mufson et al., 2000) and plays an important role in memory and attention (Crawley et al., 1996; Wrenn, 2001) and neuroplasticity (Counts et al., 2003). Basal forebrain GAL immunoreactive fibers hypertrophy and hyperinnervate remaining cholinergic neurons in the medial septal diagonal band complex (Mufson et al., 1993) and nucleus basalis in AD (Bowser et al., 1997; ChanPalay et al., 19.Ificant relationship to synaptic numbers in either lamina (Scheff et al., 1990; Scheff and Price, 1993, 2001). Recent data suggests that the amyloid toxic moiety is the oligomeric component of A (Lacor et al. 2007), which damages synapses (Lacor et al., 2007) and results in cognitive impairment (Lesne et al., 2006; Tu et al., 2014). Therefore, further clinical pathological studies are required to determine the relationship between hippocampal plasticity and the oligomeric forms of A as well as other components of proteolytically processed APP, including the C-terminal fragment of APP and other metabolites.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptHippocampal Plasticity and Brain ReserveKatzman et al., 1988, first introduced the concept of the brain reserve to explain hippocampal structural and biochemical plasticity in the course of AD. Post-mortem examinations in 137 elderly persons revealed a discrepancy between the degree of AD neuropathology and the clinical manifestations at the time of death. Some subjects whose brains had extensive AD pathology had no or very little clinical manifestations of the disease (Katzman et al., 1988). Similar results have since been reported by a number of other investigators (e.g., Mufson et al., 1999; Price et al. 2009, Markesbery et al., 2009; Mufson et al., 2014; Schneider et al., 2009). The seminal paper by Katzman et al. (1988) also reported that these persons had higher brain weights and greater number of neurons as compared to age-matched controls, leading the authors to propose two possible explanations for this phenomenon: these people may have had incipient AD but by some as-yet unknown factor avoided the loss of large numbers of neurons, or alternatively, began with larger brains and more neurons. This led to the concept of a greater brain “reserve”, which might allow for synaptic remodeling as a compensatory mechanism to the early pathobiology of the disease and in turn be able to maintain cognitive abilities in the prodromal stages of the dementia (Mufson et al., 1999; Katzman et al., 1988; Snowdon et al., 1996; Mortimer et al., 1988; DeKosky et al., 2002). It has been suggested that neuroplastic responses are lost as an individual’s dementia progresses (Mesulam, 1999) leading to the consistent observation of a reduction in neuronal viability (Gilmor et al., 1999) and activity in the hippocampus in late-Neuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagestage AD (DeKosky et al., 2002; Iknonomovic et al., 2003; Davis et al., 1999). An additional phase of plasticity, not evoked until later in the disease, is the development of a neuroplastic response by the inhibitory neuropeptide, galanin (GAL), a G-protein coupled receptor that mediates neurotransmission in the basal forebrain, entorhinal cortex, hippocampus and amygdala (Habert-Ortoli et al., 1994; Smith et al., 1998; Kolakowski et al., 1998; Dutar et al., 1989, Fisone et al., 1987; Coumis et al., 2002; Hartonian et al., 2002; Jhamandas et al., 2002; Mazarati et al., 2000; McDonald et al., 1998; Mufson et al., 2000) and plays an important role in memory and attention (Crawley et al., 1996; Wrenn, 2001) and neuroplasticity (Counts et al., 2003). Basal forebrain GAL immunoreactive fibers hypertrophy and hyperinnervate remaining cholinergic neurons in the medial septal diagonal band complex (Mufson et al., 1993) and nucleus basalis in AD (Bowser et al., 1997; ChanPalay et al., 19.
